Primary pulmonary lymphoepithelioma-like carcinoma is characterized by high PD-L1 expression, but low tumor mutation burden

Abstract

Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer (NSCLC). There are few reported studies on the relationship between programmed death ligand-1 (PD-L1) expression and genomics features of this distinct NSCLC subtype. Our study aimed to investigate the expression levels of PD-L1 to determine their clinical value and to identify genetic alterations in PLELC. Fifty-nine PLELC patients, whose clinical information and pathology results were available, were included in this study. Immunohistochemical analysis of PD-L1 was performed in all cases. Specimens of 37 PLELCs and 3 metastatic nasopharyngeal carcinomas (NPCs) of the lung, resected within the previous 3 years, were chosen for mutation analysis, using next-generation sequencing of 425 genes. PLELC patients in the present study were mainly non-smoking females, with a high frequency of PD-L1 positivity in their tumors. Positivity rates were 96.6 %, 91.5 %, 83.1 %, and 61.0 % at tumor proportion scores (TPSs)≥ 1%, 5%, 10 %, and 50 %, respectively. Moreover, we observed that PD-L1 expression was higher in specimens stored for ≤ 3 years and in tumor cells with vesicular nucleus morphology at a TPS ≥ 50 %. Mutation analysis suggested a relatively high frequency of TP53 mutations and MCL1 copy number variation, but low tumor mutation burden (TMB) (ranging from 0 to 6.9, median of 1.1 mutation per megabase) and similarity of gene alteration with NPCs. However, no specific germline mutation was detected in PLELC patients. Additionally, survival analysis showed that patients in the early stages (stage I and II) had higher progression-free survival rates (P = 0.035) and those with tumors containing obvious stroma fibrosis tended to have worse prognosis (P = 0.008). However only stage was shown to be the independent prognostic factor (P = 0.008, HR=4.807, 95 %CI:1.508-15.323).PLELC is a subtype of lung cancer with distinct clinicopathological and genetic features, especially characterized by high PD-L1 expression and low TMB.

Keywords: Next-generation sequencing; PD-L1; Pulmonary lymphoepithelioma-like carcinoma; Tumor mutation burden.